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Fosinopril and zofenopril, two angiotensin-converting enzyme (ACE) inhibitors, potentiate the anticonvulsant activity of antiepileptic drugs against audiogenic seizures in DBA/2 mice.
- Source :
-
Pharmacological research [Pharmacol Res] 2012 Mar; Vol. 65 (3), pp. 285-96. Date of Electronic Publication: 2011 Nov 17. - Publication Year :
- 2012
-
Abstract
- The renin-angiotensin system (RAS) exists in the brain and it may be involved in pathogenesis of neurological and psychiatric disorders including seizures. The aim of the present research was to evaluate the effects of some angiotensin-converting enzyme inhibitors (ACEi; captopril, enalapril, fosinopril and zofenopril), commonly used as antihypertensive agents, in the DBA/2 mice animal model of generalized tonic-clonic seizures. Furthermore, the co-administration of these compounds with some antiepileptic drugs (AEDs; carbamazepine, diazepam, felbamate, gabapentin, lamotrigine, phenobarbital, phenytoin, topiramate and valproate) was studied in order to identify possible positive interactions in the same model. All ACEi were able to decrease the severity of audiogenic seizures with the exception of enalapril up to the dose of 100mg/kg, the rank order of activity was as follows: fosinopril>zofenopril>captopril. The co-administration of ineffective doses of all ACE inhibitors with AEDs, generally increased the potency of the latter. Fosinopril was the most active in potentiating the activity of AEDs and the combination of ACEi with lamotrigine and valproate was the most favorable, whereas, the co-administrations with diazepam and phenobarbital seemed to be neutral. The increase in potency was generally associated with an enhancement of motor impairment, however, the therapeutic index of combined treatment of AEDs with ACEi was predominantly more favorable than control. ACEi administration did not influence plasma and brain concentrations of the AEDs studied excluding pharmacokinetic interactions and concluding that it is of pharmacodynamic nature. In conclusion, fosinopril, zofenopril, enalapril and captopril showed an additive anticonvulsant effect when co-administered with some AEDs, most notably carbamazepine, felbamate, lamotrigine, topiramate and valproate, implicating a possible therapeutic relevance of such drug combinations.<br /> (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Subjects :
- Angiotensin-Converting Enzyme Inhibitors administration & dosage
Angiotensin-Converting Enzyme Inhibitors therapeutic use
Animals
Anticonvulsants administration & dosage
Anticonvulsants pharmacology
Captopril administration & dosage
Captopril therapeutic use
Drug Synergism
Enalapril administration & dosage
Enalapril therapeutic use
Female
Fosinopril administration & dosage
Fosinopril therapeutic use
Male
Mice
Motor Activity drug effects
Angiotensin-Converting Enzyme Inhibitors pharmacology
Anticonvulsants therapeutic use
Captopril analogs & derivatives
Captopril pharmacology
Enalapril pharmacology
Fosinopril pharmacology
Seizures drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1096-1186
- Volume :
- 65
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Pharmacological research
- Publication Type :
- Academic Journal
- Accession number :
- 22107891
- Full Text :
- https://doi.org/10.1016/j.phrs.2011.11.005